In order to investigate certain cellular and biochemical aspects of neural development, this project uses biochemical, morphological, and physiological approaches to study the nervous system of a metamorphosing insect. Neural correlates of the various stages of development and hormonally controlled metamorphosis of the large, easily reared moth Manduca sexta will be scrutinized with three immediate objectives: 1) to describe the sequence of cellular changes in the developing antennae and central nervous system; 2) to study the specification and development of selected neurotransmitter systems (e.g. acetylcholine) and to correlate these biochemical events with the cellular changes; and 5) to try to understand when, in what order, and under what influences the various structural, biochemical, and physiological characteristics of neurons develop in vivo. Cellular events will be studied with histological, autoradiographic, and electrophysiological methods in order to examine the origin, specification, growth, and maturation of neurons. Sensitive radiochemical and spectrophotometric assays will be combined with histochemistry for studies of neurotransmitter systems in developing neurons and regions of the nervous system. Microsurgical, hormonal, pharmacological, and in vitro culture techniques will be used for studies of molecular and cellular influences that govern neural and neuromuscular development. It is hoped that these investigations of an appropriate invertebrate preparation will contribute directly to our understanding of neural development in general, including that in man. BIBLIOGRAPHIC REFERENCES: Sanes, J.R., and Hildebrand, J.G. (1976). "Origin and morphogenesis of sensory neurons in an insect antenna" Devel. Biol. in press. Sanes, J.R., Hildebrand, J.G., and Prescott, D.J. (1976). "Differentiation of insect sensory neurons in the absence of their normal synaptic targets," Devel. Biol. in press.